The study compares the impact of freeze- and spray-drying (FD, SD) microencapsulation methods on the content of β-glucan, total polyphenols (TP), total flavonoids (TF), phenolic acids (PA), and antioxidant activity (AA) in commercially β-glucan powder (Pleurotus ostreatus) using maltodextrin as a carrier. Morphology (scanning electron microscopy- SEM), yield, moisture content (MC), and water activity (a_w) were also evaluated in the samples. Our examinations revealed significant structural differences between powders microencapsulated by the drying methods. As compared to non-encapsulated powder, the SD powder with yield of 44.38 ± 0.55% exhibited more reduced (p < 0.05) values for a_w (0.456 ± 0.001) and MC (8.90 ± 0.44%) than the FD one (yield: 27.97 ± 0.33%; a_w: 0.506 ± 0.002; MC: 11.30 ± 0.28%). In addition, the highest values for β-glucan content (72.39 ± 0.38%), TPC (3.40 ± 0.17 mg GAE/g), and TFC (3.07 ± 0.29 mg QE/g) have been detected in the SD powder. Our results allow for the conclusion that the SD microencapsulation method using maltodextrin seems to be more powerful in terms of the β-glucan powder yield and its contents of β-glucan, TP, and TF as compared to the FD technique.